A stem cell is a cell capable of being differentiated into various cells configuring biological tissues, and includes all of undifferentiated cells in steps before being differentiated, obtainable from each tissue of embryos, fetuses and adults. Among various stem cells, a pluripotent stem cell refers to a stem cell having poly-functionality which is capable of being differentiated into all of three germ layers configuring a living body.
The stem cell may be divided into an embryonic stem cell (ES cell) that is separated from embryo, and an adult stem cell that is separated from an adult, depending on separated objects. In addition, the stem cell may be divided into a pluripotent stem cell, a multipotent stem cell, and a unipotent stem cell according to the number of differentiated cells created from one stem cell. In general, an embryonic stem cell (ES cell) may be included in the pluripotent stem cell, an adult stem cell may be included in the multipotent stem cell and the unipotent stem cell.
It is known that micro RNA (miRNA) is a short single-stranded ribonucleic acid (RNA) having 19 to 25 nucleotides in length, and is expressed in cells to control expression of a number of genes (Bartel D. P., (2004) Cell, 116(2):281-97; He L. and Hannon G. J., (2004) Nat. Rev. Genet., 5(7):522-31). Until now, approximately 700 species of miRNAs are found in a human. Since one miRNA is possible to control various kinds of mRNAs, it is predicted that about 30% of human genes are regulated by miRNA (see Bentwich, et al., Nat. Rev. Genet., 37(7):766-70, 2005; Berezikov, et al., Cell, 120(1):21-4, 2005; Lewis, et al., Cell, 120(1):15-20, 2005; Krek, et al., Nat. Genet., 37:495-500, 2005; Friedman, et al., Genome Res., 19:92-105, 2009). let-7 miRNA is one of miRNA, and related to generation of embryo, occurrence of cancer cell, and the like. When the let-7 miRNA is not normally created or does not properly function, problem may occur in an embryonic development process, and cancer may be developed. U.S. Patent Laid-Open Publication No. 2006/0189557 discloses a method for treating cancer by introducing let-7 miRNA into a cancer cell to inhibit activity of RAS oncogene.
LIN28A is a conserved RNA-binding protein, and an expression thereof is strictly regulated in an animal developmental process. LIN28A plays an important role in the generation and particular diseases. For example, LIN28A is highly expressed in embryonic stem cells, and is one of four factors required for changing fibroblasts in humans or mice to induced pluripotent stem cells (iPSCs). A mechanism in which LIN28A is activated in the nucleus has not been found so far.